Recently, the Centers for Disease Control and Prevention publicized findings from the largest US study performed on dental health in 25 years indicating that while oral health is improving for most Americans, tooth decay among preschool children (between the ages of 2 and 5 years old) increased from 24% (between 1988-1994) to 28% (between 1999-2004). Of the types of oral formulations, mouthrinses are especially appealin not only because of simplicity and convenience but also for high-risk caries groups including those with orthodontic brackets and retainers, prostheses and restorations, dental erosion, children with developing permanent dentition, and those experiencing hyposalivation caused by medications and/or cancer treatments. Published studies reveal that multi-mineral treatments, including fluoride, calcium, and phosphorous can act synergistically to provide enhanced levels for protection compared to single mineral treatments. However, a major problem facing multi-mineral formulations, however, is that bioavailable fluoride and calcium cannot coexist in a single stable formulation for long periods of time, which ultimately reduces the shelf-life and therapeutic performance of the multi-mineral formulation. Because of the sensitivity of fluoride, currently there is no single-compartment multi-mineral mouthrinse available commercially in the US. Indiana Nanotech has patent- pending technology that functionalizes 2-tricalcium phosphate (TCP) with sodium lauryl sulfate (SLS) to create TCP-SLS hybrid materials that are compatible with fluoride. Importantly, when combined in an established and commercially available OTC fluoride mouthrinse formulation, TCP-SLS boosted enamel fluoride uptake (~ 25%) and strengthened enamel 'white-spots' (~ 50%) relative to the commercial OTC fluoride mouthrinse. The long-term goal of this research is to commercialize an economical OTC multi-mineral mouthrinse formulation that provides increased dental health benefits than would otherwise be observed with fluoride alone. As part of our development and commercialization activities, we have developed this Phase II research proposal to the NIDCR that addresses the following Specific Aims: 1) Evaluation of stability and in vitro efficacy of NaF mouthrinse formulations containing TCP-SLS. These activities include FDA- recommended laboratory studies, including fluoride bioavailability, enamel fluoride uptake, and white-spot lesion reversal via remin/demin cycling; 2) understand the remineralization effect of TCP-SLS. This will include extending our current understanding of TCP-SLS by probing the bonding and interface characteristics of TCP-SLS, as well the enamel tissue that is treated with TCP-SLS and fluoride; and 3) Evaluation of the most promising prototype mouthrinse formulation against a commercially available fluoride mouthrinse rinse in a placebo-controlled double-blind cross-over in situ clinical study.